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INTRODUCTION: Outcomes from diabetic foot infections (DFIs) at the major referral hospital (Hospital Nacional de San Benito) in El Petén, Guatemala have not been analyzed. We hypothesized that poor diabetic control might be associated with a high rate of major lower extremity amputations (mLEAs; above the ankle). METHODS: We performed a retrospective analysis at Hospital Nacional de San Benito between (8/14 and 6/23) in patients presenting with DFIs. Patients receiving mLEAs were compared with all others (AO = [trans-metatarsal amputations, toe amputations, incision and drainage, and antibiotic treatment]). Interviews surgeons were undertaken to ascertain reasons for index operation choice. Univariable and multivariable analyses were undertaken to determine factors associated with mLEAs. RESULTS: Of 110 patients with DFIs, there were 23 mLEAs (above the knee = 21, below the knee = 2). Age, duration with diabetes, and a prior ipsilateral minor amputation were associated with mLEAs. Multivariable analysis identified white blood cell count as significant for mLEA (odds ratio = 1.5 95% confidence interval [1.0 to 2.5]). Cited reasons for a high rate of above the knee amputation (AKAs) versus below the knee amputation were patient related (advanced disease, patient frailty, and poor compliance), systemic (lack of vascular equipment and knee immobilizer), and surgeon related. CONCLUSIONS: This cohort of patients presented with an average of 15 years with diabetes mellitus and poor adherence to diabetic treatment (40%). Many of these diabetic patients developed a DFI requiring mLEAs (21%), most of which were AKAs (91%). Efforts to minimize the number of AKA versus below the knee amputation require immediate attention. Programs to adhere to DM control and foot care in patients with DM are urgently needed.
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This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM). METHODS: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM. RESULTS: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN. CONCLUSION: The review presents a possible relationship between DPN and CAN, such as in their severity.
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Doenças do Sistema Nervoso Autônomo , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Humanos , Diabetes Mellitus Tipo 2/complicações , Doenças do Sistema Nervoso Autônomo/epidemiologia , Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/complicações , Cardiomiopatias Diabéticas/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.
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Glicemia , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Glucagon , Teste de Tolerância a Glucose , Condução Nervosa , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Masculino , Pessoa de Meia-Idade , Feminino , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/etiologia , Glucagon/sangue , Estudos Retrospectivos , Glicemia/análise , Condução Nervosa/fisiologia , Idoso , Adulto , Eletromiografia , Células Secretoras de Glucagon , Insulina/sangue , Área Sob a Curva , Fatores de Tempo , Valores de ReferênciaRESUMO
OBJECTIVE: Peripheral neuropathy (PN) is one of the most common diseases of the peripheral nervous system. Symptoms range from mild sensory signs to severe neuropathic pain. Untreated PN is progressive and can lead to complications and impair quality of life (QoL). However, PN prevalence is underestimated in the general population and affected individuals often remain undiagnosed. This study aimed to contribute to the global generation of prevalence data and determine sociodemographic and disease-related characteristics of PN sufferers. METHODS: This cross-sectional study collected information on PN prevalence and associated factors in the adult population (40-65 years) of the Mexico City area. Participants were recruited in public places and screened for PN using the Michigan Neuropathy Screening Instrument (MNSI). Subjects with PN answered the Neuropathy Total Symptom Score-6 (NTSS-6), the Short Form-36 Health Survey (SF-36), and the QoL Pharmacoeconomic Questionnaire. Statistical analysis included descriptive methods and calculation of PN prevalence with 95% confidence intervals. RESULTS: Of 3066 participants, 448 had PN based on the MNSI physical examination. The overall PN prevalence was 14.6%, with the highest (18.9%) seen in subjects aged 61-65 years. PN was undiagnosed in 82.6%, and 62.9% had never heard of PN. Although half of all subjects had only mild PN symptoms, QoL was impacted in 91.8%. CONCLUSIONS: The results confirm that PN prevalence in the general population is high. Despite the disease burden, most affected persons are undiagnosed and unaware of the disease. Almost all felt their QoL was impacted. The data highlight the need to raise awareness and identify undiagnosed individuals to prevent complications.
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INTRODUCTION: Diabetes mellitus (DM) is a metabolic disorder characterized by an abnormal increase in blood glucose levels resulting from insulin secretion and/or dysfunctional activity that can lead to several serious complications in addition to decreased postural balance. OBJECTIVE: This study aimed to identify and analyze the main interventions used to improve static balance in patients with DM. METHODS: For the selection of articles, a bibliographic search was performed using PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Only clinical trials that investigated the effect of training on static balance in adults with type 2 DM were selected, and 34 studies were included. RESULTS: The search resulted in the identification of 2681 articles, and of these, 31 were eligible for the study. The identified interventions were proprioceptive, aerobic, resistance training on platforms, in virtual reality, and Tai Chi. The main results obtained were an increase in time in the one-leg stance, Romberg test, and tandem position, a significant increase in the Berg Balance Scale score and balance index, and a reduction in the variables of postural sway. CONCLUSION: There are a variety of effective training methods for improving static balance, and the choice of intervention to be applied goes beyond proven effectiveness, depending on reproducibility and/or financial cost.
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Diabetes Mellitus Tipo 2 , Equilíbrio Postural , Humanos , Equilíbrio Postural/fisiologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/fisiopatologia , Treinamento Resistido/métodos , Terapia por Exercício/métodos , Tai Chi Chuan/métodos , Exercício Físico/fisiologiaRESUMO
Abstract Background: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). Methods: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. Results: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. Conclusion: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.
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Oxaliplatin (OXA) is an antineoplastic agent used for the treatment of cisplatin-resistant tumours, presenting lower incidence of nephrotoxicity and myelotoxicity than other platinum-based drugs. However, OXA treatment is highly associated with painful peripheral neuropathy, a well-known and relevant side effect caused by mitochondrial dysfunction. The transfer of functional exogenous mitochondria (mitotherapy) is a promising therapeutic strategy for mitochondrial diseases. We investigated the effect of mitotherapy on oxaliplatin-induced painful peripheral neuropathy (OIPN) in male mice. OIPN was induced by i.p. injections of oxaliplatin (3 mg/kg) over 5 consecutive days. Mechanical (von Frey test) and cold (acetone drop test) allodynia were evaluated between 7 and 17 days after the first OXA treatment. Mitochondria was isolated from donor mouse livers and mitochondrial oxidative phosphorylation was assessed with high resolution respirometry. After confirming that the isolated mitochondria were functional, the organelles were administered at the dose of 0.5 mg/kg of mitochondrial protein on days 1, 3 and 5. Treatment with OXA caused both mechanical and cold allodynia in mice that were significant 7 days after the initial injection of OXA and persisted for up to 17 days. Mitotherapy significantly prevented the development of both sensory alterations, and attenuated body weight loss induced by OXA. Mitotherapy also prevented spinal cord ERK1/2 activation, microgliosis and the increase in TLR4 mRNA levels. Mitotherapy prevented OIPN by inhibiting neuroinflammation and the consequent cellular overactivity in the spinal cord, presenting a potential therapeutic strategy for pain management in oncologic patients undergoing OXA treatment.
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Antineoplásicos , Dor , Doenças do Sistema Nervoso Periférico , Humanos , Masculino , Camundongos , Animais , Oxaliplatina/toxicidade , Hiperalgesia/induzido quimicamente , Hiperalgesia/prevenção & controle , Hiperalgesia/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Antineoplásicos/toxicidadeRESUMO
The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca2+-ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mice without affecting locomotion or exploration. MTDZ also modulated multiple pathways, including glutamatergic, NO/L-arginine/cGMP, serotonergic (5-HT1A/1B), opioid, and TRPV1 pathways. Additionally, MTDZ reduced NOx levels and modulated Ca2+-ATPase activity. In conclusion, MTDZ effectively alleviated PTX-induced peripheral neuropathy and demonstrated multi-targeted modulation of pain-related pathways. Its ability to modulate multiple pathways, reduce NOx levels, and modulate Ca2+-ATPase activity makes it a potential pharmacological candidate for peripheral neuropathy, acute nociceptive, and inflammatory conditions. Further research is needed to explore its therapeutic potential in these areas.
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BACKGROUND: Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapy-induced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health-Related Quality of Life (HRQoL) and activities of daily living (ADL). OBJECTIVE: We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. METHODS: This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. RESULTS: In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. CONCLUSION: MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.
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BACKGROUND AND AIMS: Multifocal motor neuropathy (MMN) is a peripheral nerve disorder characterized by slow progressive distal asymmetric weakness with minimal or no sensory impairment. Currently, a vast evidence supports a direct pathogenic role of IgM anti-GM1 antibodies on disease pathogenesis. Patients with MMN seropositive for GM1-specific IgM antibodies have significantly more weakness, disability and axon loss than patients without these antibodies. During the screening for IgM anti-GM1 antibodies in a cohort of patients with neuropathy we noticed an absence or significant reduction of natural IgM anti-GM1 autoreactivity in some patients with MMN, suggesting a mechanism of self-control of autoreactivity. We aim to understand the lack of natural reactivity against GM1 in MMN patients. METHODS: The presence of free IgM anti-GM1 reactivity or its complex to blocking IgG was analysed by combining high performance thin layer chromatography-immunostaining, soluble binding inhibition assays, Protein-G or GM1-affinity columns and dot blot assays. RESULTS: We identified in MMN patients an immunoregulation of IgM anti-GM1 antibodies mediated by IgG immunoglobulins characterized by: (i) lack of natural IgM anti-GM1 autoreactivity as a result of a immunoregulatory IgG-dependent mechanism; (ii) presence of natural and disease-associated IgM anti-GM1/IgG blocking Ab complexes in sera; and (iii) high levels of IgG blocking against natural IgM anti-GM1 antibodies (Abs. INTERPRETATION: Our observations unmask a spontaneous IgG-dependent mechanism of immunoregulation against IgM anti-GM1 antibodies that could explain, in part, fluctuations in the usually slowly progressive clinical course that characterizes the disease and, at the same time, allows the identification of an autoimmune response against GM1 ganglioside in seronegative patients.